Microglia are resident macrophages in the central nervous system (CNS). They become activated upon injury or infection in the CNS. Theiler's murine encephalomyelitis virus (TMEV) infection causes development of an autoimmune demyelinating disease in the CNS of SJL mice. TMEV induced demyelinating disease has been identified as a model for multiple sclerosis in humans. The two diseases share several similarities. Previous studies have shown that microglia are present in the early lesions of both of these demyelinating diseases This study proposes to determine the role of microglia in the initiation and continuation of the demyelinating disease. First, microglia will be studied to determine their role in viral persistence which leads to the demyelinating disease in the CNS. Second, the role of microglia as antigen presenting cells during the viral infection will be examined to determine whether microglia present viral epitopes. The initial immune response leads to tissue damage and the initiation of the autoimmune response against myelin proteins. Next, the ability of microglia to present myelin epitopes will be studied for their role in the exacerbation of the demyelination. Thus, this study will determine the various roles microglia as resident macrophages in the CNS may play in TMEV induced autoimmune demyelinating disease.